Feng Yu, Zhao Qian, Zhao Yifan, Ma Chen, Tian Meiling, Hu Xiaosong, Chen Fang, Li Daotong
Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Engineering Research Centre for Fruits and Vegetable Processing, Ministry of Agriculture, Ministry of Education, China Agricultural University, Beijing, 100083, China.
College of Food Science and Nutritional Engineering, China Agricultural University, No. 17, Qinghua East Road, Haidian District, Beijing, 100083, China.
J Nanobiotechnology. 2025 Jun 7;23(1):426. doi: 10.1186/s12951-025-03504-w.
Inflammatory bowel disease (IBD) is a gastrointestinal inflammatory disorder characterized by disturbed interactions between gut microbiota and host immune response. Barley leaf (BL) is a traditional Chinese herb recorded to have health-promoting effects. However, little is known about the beneficial role of BL against enteric infection-induced intestinal inflammation. Here, we uncover that BL protects against Citrobacter rodentium (C. rodentium)-induced infectious colitis by improving host-microbiota interactions.
C3H/HeN mice were fed a diet with/without BL and infected with C. rodentium. Transcriptome sequencing, anti-CD4 antibody treatment, and flow cytometry were conducted to investigate the mechanisms of T cell immune modulation. The intervention involved administering anti-CD4 antibody at 500 µg each time for three times before and during C. rodentium infection. Analysis of gut microbiota composition was performed by 16S rRNA gene sequencing on fecal samples. Fecal microbiota transplantation was conducted by administering microbiota from donor group to recipient group via oral gavage to investigate the role of intestinal microbiota in immune modulation.
BL ameliorated the severity of C. rodentium-induced colitis, and this effect was linked to improved gut homeostasis and enhanced mucosal barrier function. BL enriched the pathways of T helper 1 (Th1)/Th2 and Th17 cell differentiation in the colon, suggesting the involvement of CD4 T cells. Consistent with this, anti-CD4 antibody treatment abrogated the effect of BL and flow cytometry analysis revealed that BL mitigated C. rodentium-induced pro-inflammatory Th1 immune response. Moreover, the protective effect of BL was associated with alleviation of gut microbiota dysbiosis and increased abundance of Lactobacillus. Our in vivo studies further revealed that live Lactobacillus plantarum (L. plantarum) administration attenuated the pathogenic effects induced by C. rodentium infection, whereas heat-inactivated L. plantarum did not show the same results. Mechanistically, BL supplementation enriched L. plantarum, which subsequently released nanosized extracellular vesicles (EVs) that serve as a key mediator in alleviating C. rodentium-associated pathology and Th1 cell dysregulation.
Our work thus provides evidence for utilizing BL and L. plantarum-derived EVs to manage enteric infection-associated IBD.
炎症性肠病（IBD）是一种胃肠道炎症性疾病，其特征是肠道微生物群与宿主免疫反应之间的相互作用紊乱。大麦叶（BL）是一种有促进健康作用记载的传统中草药。然而，关于BL对肠道感染诱导的肠道炎症的有益作用知之甚少。在此，我们发现BL通过改善宿主 - 微生物群相互作用来预防鼠柠檬酸杆菌（C. rodentium）诱导的感染性结肠炎。
给C3H/HeN小鼠喂食含/不含BL的饮食，并感染鼠柠檬酸杆菌。进行转录组测序、抗CD4抗体治疗和流式细胞术以研究T细胞免疫调节机制。干预措施是在鼠柠檬酸杆菌感染前及感染期间每次给予500μg抗CD4抗体，共三次。通过对粪便样本进行16S rRNA基因测序来分析肠道微生物群组成。通过经口灌胃将供体组的微生物群给予受体组进行粪便微生物群移植，以研究肠道微生物群在免疫调节中的作用。
BL减轻了鼠柠檬酸杆菌诱导的结肠炎的严重程度，这种作用与改善肠道稳态和增强黏膜屏障功能有关。BL丰富了结肠中辅助性T细胞1（Th1）/Th2和Th17细胞分化的途径，提示CD4 T细胞参与其中。与此一致，抗CD4抗体治疗消除了BL的作用，流式细胞术分析显示BL减轻了鼠柠檬酸杆菌诱导的促炎性Th1免疫反应。此外，BL的保护作用与减轻肠道微生物群失调和乳酸杆菌丰度增加有关。我们的体内研究进一步表明，给予活的植物乳杆菌（L. plantarum）可减轻鼠柠檬酸杆菌感染诱导的致病作用，而热灭活的植物乳杆菌则未显示相同结果。从机制上讲，补充BL可富集植物乳杆菌，其随后释放纳米级细胞外囊泡（EVs），这些囊泡是减轻鼠柠檬酸杆菌相关病理和Th1细胞失调的关键介质。
因此，我们的工作为利用BL和植物乳杆菌来源的EVs来治疗肠道感染相关的IBD提供了证据。
